General Acid-Base Catalysis by OH Groups

Another important pioneering work in CyD chemistry was reported by Breslow and Campbell [7] on the chlorination of anisole with HOCl. In the presence of a-CyD, the chlorination occurs exclusively at the para-position of anisole. This reaction also takes advantage of covalent catalysis. Here, HOCl first reacts with the secondary OH group of CyD, and the chlorine atom is selectively transferred to the para-position of anisole. Since the anisole penetrates into the cavity with the methoxy group first, the para-position of anisole is located near the secondary OH group (and thus near the CyD-OCl group). Apparently, the product selectivity comes from a proximity effect , as is often observed in enzymatic reactions. 

Hydrolysis of alkyl esters by CyD proceeds via general base catalysis by CyD-0 [8], which is in contrast with nucleophilic catalysis by CyD (dired attack by CyD-0 to the substrate) in the hydrolysis of aryl esters (see above). The leaving groups of alkyl esters (alkoxide ions) are too poor to be removed from the tetrahedral intermediate formed by the nucleophilic attack by Cy D-0 . Thus, as an alternative way, CyD-0 activates the water in solutions by general base catalysis and this activates the attacks of water towards the substrate. 

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All the reactions catalyzed by CyDs (and by their derivatives) proceed via their complexes with substrates, in which the chemical transformation takes place. This reaction scheme is exactly parallel to that employed by naturally occurring enzymes, and both high specificity and large reaction rates are primarily associated with this reaction scheme. Catalyses by CyDs are divided into three categories (1) covalent catalysis in which a covalent intermediate is first formed from CyD and substrate and this intermediate is converted to the final products in the following step, (2) general acid-base catalysis by OH groups, and (3) non-covalent catalysis in which CyDs participate in the reactions only in a noncovalent fashion without even proton-transfer processes. The number of papers on catalysis by CyDs has... 

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